It has been demonstrated that CD8 positive CTLs recognize epitope peptides derived from tumor-associated antigens (TAAs) found on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPLs 1, 2). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development and clinical investigation of peptide vaccination strategies for various types of cancer is ongoing (NPLs 3 to 10). To date, several clinical trials using these TAA derived peptides have been reported. Unfortunately, many of the current cancer vaccine trials have shown only a low objective response rate (NPLs 11 to 13). Therefore, identification of novel TAAs useful as immunotherapeutic targets is still required.
To that end, through gene expression profiling with a genome-wide cDNA microarray containing 23,648 genes, TMEM22 (GenBank Accession No. NM—025246, NM—001097599, NM—001097600), transmembrane protein 22, has been identified as a transmembrane protein associated with cell growth of renal cell carcinoma (RCC) (NPL 14). Northern blot analysis has confirmed the expression TMEM22 to be specifically up-regulated in a great majority of RCC clinical samples and cell lines examined, with only barely detectable expression in normal human tissues examined. Furthermore, down-regulation of TMEM22 expression by specific siRNA has been shown to result in significant reduction of RCC cell growth (NPL 15). However, the pathophysiological role and biological function of TMEM-22 in the context of cancer cells have not yet been reported.